Pharmokinetics / pharmacodynamics Flashcards
Partition coefficient (lipid/water)
dissolve drug in water, add equal volume fat, see where drug separates
[oil] / [water] = coefficient
Aspirin ionization
Gets deionized in the stomach (carboxyl group)
Reionized in intestine, then can’t leave
How long for a drug to be available all over the body once in the blood?
~120 sec
Mana said ‘within a minute’
Pharmacodynamics
Study of biochemical and physical effects of drugs
binding to effector proteins
What is depot binding?
When drugs bind to other proteins / tissues (e.g. fat, bone marrow, etc)
If a drug binds to bone marrow, what happens in terms of concentration, etc?
Drug stays in the body longer
Less drug at the intended site of action
How / where are most drugs inactivated?
The liver
Broken down / altered by enzymes
Is glucose a drug?
No.
Drug = non-nutritive chemical that alters physiology
If you alter the sympathetic nervous system but not the CNS with a chemical, is that a psychoactive drug?
No. Chemicals must get through the BBB and get into the CNS to be considered a drug.
What is pharmacokinetics?
How drugs move around.
How they’re administered, where they go once you administer them, how they’re metabolized, how they leave the body
pharmacokinetic binding
The exact way in which a drug attaches to a receptor, pump, enzyme, etc.
How are drugs inactivated in metabolism?
increase polarity of drug so that it can’t go through stuff
Lots of other stuff
What is the most common route of drug administration?
What are the advantages / disadvantages?
Oral: safe, don’t need help
Problems: all kinds of things can change how fast you absorb it. Hard to predict
First-pass metabolism
What is the vomiting area of the medulla called?
How does it determine vomiting?
area postrema
Area in the medulla with no BBB
Samples blood to determine if you should throw up
What are some other ways to get drugs in your body?
ICV (intraventricularly): directly into brain
IV (intravenous): into blood
IM (instramuscularly): Localized at injection site.
How fast are the effects of inhalation?
Almost immediate - heavily vascularized, thin membranes in the lungs
Every molecule has the chance to go to brain before liver
What is first-pass metabolism?
Drug gets metabolized in the liver for excretion before it does other stuff
What is the ‘vehicle’ for a drug?
The medium through which it’s delivered
Why is rectal administration useful?
Lower third of digestive system doesn’t suffer from first-pass problems (doesn’t pass through liver)
Huge absorptive surface there
What is the route for first-pass metabolism?
Anything that goes through liver (up to 20-30% of drug inactivated before it gets to brain)
How much total drug movement is there for aspirin in stomach vs. small intestine?
More in small intestine, BECAUSE of absorptive surface!
With same amount of absorptive surface, stomach would be better
What does a drug need to get into the CNS?
Small, lipid-soluble, or transported
What are platelets? What do they relate to?
Proteins found in blood
Depot binding - psychoactive drugs can bind to them instead of go into CNS
What do liver enzymes do?
Break the drug down (change it structurally so that it can’t bind)
Normally make more water soluble
What are metabolites?
Active metabolites?
Products of a liver enzyme. Has been chemically changed somehow
Active: Exert psychoactive effects after becoming metabolites
What happens in phase II metabolism?
You add stuff - change structure so that it can’t bind to stuff. New functional groups
What happens in Phase I metabolism?
Oxidation / reduction
Structure isn’t changed though (as in, new functional groups don’t get added)
Where are polar drug species excreted?
Urine (‘renal elimination’)
Where are nonpolar drug species excreted?
Feces (‘biliary elimination’)
What is cross-tolerance?
e.g. history of cigarette smoking causes ethanol tolerance
The same enzyme metabolizes two drugs, so taking one drug helps with metabolism of the other
What is zero-order kinetics?
Rate of metabolism is constant / linear
What is first-order kinetics?
Rate of metabolism greater with more plasma levels - exponential decrease
What is the half-life?
Time it takes for drug to eliminate to 1/2 of its peak plasma level
What does the half-life look like with zero-order kinetics?
Half-life decreases with decreasing concentration
What does the half-life look like with first order kinetics?
Length of half-life is constant
Specific vs. nonspecific drug effects
Specific: effects based on interactions of a drug with target tissue
Nonspecific: based on characteristics of the individual taking the drug, not on the drug’s interactions with target tissue (e.g. mood at the time, diet, etc)
Example of nonspecific drug effect?
e.g. placebo
What are enteral methods of drug administration?
Use the gastrointestinal tract to get agents in the body
What kinds of enteral administration are there?
oral, through rectal cavities
What is the opposite of enteral administration?
parenteral
e.g. injection, pulmonary, topical administration
topical administration
administration to body surface
What are four effects of depot binding?
- Drugs stay in tissue longer
- Drugs that compete for depots could be displaced
- onset of action could be delayed
- Depots could be responsible for termination e.g they go to CNS first, but then depots change blood/brain concentration difference and cause them to leave cns faster
What are microsomal enzymes and where are they found?
Liver enzymes that metabolize psychoactive drugs
Found in smooth ER of liver cells
What class of microsomal enzyme is responsible for metabolizing most psychoactive drugs?
Cytochrome P450 (CYP450)
What is Kd in relation to pharmacodynamics?
Affinity of drug for receptor.
Kd = [drug][receptors] / [drug + receptors]
Drug + target –> Drug-target complex
If you have a higher Kd, what happens to the drug’s affinity for a receptor?
Drug has less affinity for receptor (higher concentration of drug/receptor individually)
What is the term for how well a ligand activates a receptor / produces a functional response?
intrinsic activity
What is the magnitude of a drug’s effects called?
Potency
What makes a drug more potent?
affinity and intrinsic activity
What is an inverse agonist? How is it different than an antagonist?
An inverse agonist actively creates a negative response (has effects by itself)
An antagonist simply prevents a positive response (can’t have an effect by itself)
What is the drug dose generally described in terms of?
Weight of drug / weight of recipient
in a given volume of vehicle
What is the ED50 of a dose response curve?
The dose at which 50% of people taking the drug have the response that specific curve is measuring
What two things do you need on a good dose response curve?
One dose at 0, so you know where there’s no effect
A second dose past the asymptote, so that you know there is an asymptote
What is the therapeutic window for a drug defined as?
You’re past the ED10 of the therapeutic effect
You’re before the ED10 of the toxic effect
What drugs make up the stimulants?
Amphetamine
Cocaine
Nicotine
What drugs make up the depressants?
Barbituates
Alcohol
What drugs make up the analgeisics?
Morphine
Codeins
What drugs make up the hallucinogens?
Mescaline
LSD
Psilocybin
What drugs make up the psychotherapeutics?
Prozac
Thorazine
Synergistic drug effects
Both drugs together cause a greater overall effect
Additive effects or potentiation
Antagonistic drug effects
Both drugs together cause decreased effect
Drug code names
e.g. Ro 5-2807
5 = general structure Ro = company 2807 = iteration of it
decongestant
Shrink swollen blood vessels
What is a pharmacological activity classification?
Classify drugs according to primary pharmacological activity
But there can be multiple effects
What effect of a compound is used mainly to classify them?
The compound’s therapeutic use
Do you want a high or low TI?
High
More TI = you can take more of the drug without worrying about a bad side effect
Safer drug
What is TI?
Therapeutic index
Ratio of LD50 to ED50 (lethal dose to effective dose)
What is oral administration?
Take by mouth
What is intravenous administration?
Put in veins (depleted O2)
What is intraperitoneal administration?
Put drugs into the body cavity
What is subcutaneous administration?
Put drugs directly under skin
What is intramuscular injection?
Into the muscles
